Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microcatheterization was used to study the effect of renal arterial infusion of acetylcholine or secretin on medullary collecting duct function in anaesthetized rats. Acetylcholine infusion was associated with natriuresis and increased sodium delivery to, and decreased reabsorption in, the collecting duct. No changes from control function were found with secretin. Renal blood flow was increased with acetylcholine (+82%, p less than 0.001), but unchanged with secretin (+15%, nonsignificant). We conclude that acetylcholine natriuresis is due to inhibition of tubular reabsorption of sodium in the medullary collecting duct, as well as in upstream nephron segments. While the latter may be hemodynamically mediated, the former indicates a direct transport effect of the hormone in the terminal nephron segment.
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PMID:Effect of acetylcholine and secretin on medullary collecting duct function in the rat. 395 44

Micropuncture techniques have been used to examine electrolyte secretion by the in vitro rabbit pancreas. The concentration profiles of the major secreted ions and digestive protein and the electrical potential profile within the pancreatic ductal system have been determined during spontaneous and secretin-stimulated secretion. The active transport of both Na and HCO(3) are the rate-controlling steps in primary secretion. Spontaneous secretion is produced primarily within the intralobular ducts. The anion composition of this primary secretion depends on the secretion rate with HCO(3) ranging from about 70 meq/liter at low rates to about 110 meq/liter at high rates. With secretin stimulation the smaller extralobular ducts also secrete and this extralobular secretion has a higher HCO(2) content than that of the intralobular secretion. In the main collecting duct the anion composition of the juice is modified further by Cl-HCO(3) exchange which appears to be a passive process depending on the average residence time of the juice in the main duct.
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PMID:A micropuncture investigation of the whole tissue mechanism of electrolyte secretion by the in vitro rabbit pancreas. 475 48

The gastrointestinal functions of the 27-amino acid secretin peptide have been well established. In previous prenatal studies, secretin expression in the rat duodenum was reported after day 17 of gestation while its expression in other organs and its functions in the developing embryos are still unknown. By in situ hybridization and immunohistochemical staining, secretin transcripts and peptides were found to be widely expressed in mouse embryos. Consistent with the idea that secretin is a brain-gut peptide, its expressions are present in several developing brain regions such as cephalic mesenchyme, cerebellar primordium and choroid plexus as well as the epithelial villi lining and inner circular muscle of the developing intestine. Other than these organs, secretin was also detected in the developing heart including the ventricular epicardium and myocardium and certain structures of the developing kidney like ureteric bud, collecting duct and glomerulus. These observations strongly suggest for a functional role of secretin during mouse embryonic development.
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PMID:Secretin, a known gastrointestinal peptide, is widely expressed during mouse embryonic development. 1566 52

Secretin is a classical gastrointestinal peptide while its neuroactive functions in the central nervous system have recently been consolidated. In the past, there was little information regarding the expression of secretin receptor in prenatal development. In this article, using mouse embryos and by in situ hybridization, secretin receptor transcripts were detected in several developing brain regions including the cerebellar primordium and choroid plexus. In the developing intestine, secretin receptor is present in the epithelial lining of the villi and the inner circular muscle. Interestingly, the transcripts for secretin receptor were also detected in the epicardium and myocardium of the developing heart as well as the glomerulus and collecting duct in the developing kidney. Taken together, our data suggest a potential pleiotrophic role of secretin during embryonic development.
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PMID:The prenatal expression of secretin receptor. 1688 25

The maintenance of body water homeostasis depends on the balance between water intake and water excretion. In the kidney, vasopressin (Vp) is a critical regulator of water homeostasis by controlling the insertion of aquaporin 2 (AQP2) onto the apical membrane of the collecting duct principal cells in the short term and regulating the gene expression of AQP2 in the long term. A growing body of evidence from both in vitro and in vivo studies demonstrated that both secretin and oxytocin are involved as Vp-independent mechanisms regulating the renal water reabsorption process, including the translocation and expression of AQP2. This review focuses on how these two hormones are potentially involved as Vp-independent mechanisms in controlling water homeostasis.
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PMID:Vasopressin-independent mechanisms in controlling water homeostasis. 1931 28

X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI.
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PMID:Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice. 2582 53

A growing body of evidence suggests that secretin (SCT) is an important element in the osmoregulatory pathway. It is interesting to note that both SCT and its receptor (SCTR) gene are activated upon hyperosmolality in the kidney. However, the precise molecular mechanisms underlying the induction of the SCTR gene expression in response to changes in osmolality have yet to be clarified. Detailed DNA sequence analysis of the promoter regions of the SCTR gene reveals the presence of multiple osmotic response elements (ORE). The ORE is the binding site of a key osmosensitive transactivator, namely, the nuclear factor of activated T-cells 5 (NFAT5). SCTR and NFAT5 are co-expressed in the kidney cortex and medulla collecting duct cells. We therefore hypothesize that NFAT5 is responsible for modulating SCTR expression in hypertonic environments. In this study, we found hypertonicity stimulates the promoter activities and endogenous gene expression of SCTR in mouse kidney cortex collecting duct cells (M1) and inner medulla collecting duct cells (mIMCD3). The overexpression and silencing of NFAT5 further confirmed it to be responsible for the up-regulation of the SCTR gene under hypertonic conditions. A significant increase in the interaction between NFAT5 and the SCTR promoter was also observed following chromatin immunoprecipitation assay. In vivo, osmotic stress up-regulates the SCTR gene in the kidney cortex and medulla of wild-type mice, but does not do so in NFAT5(+/-) animals. Hence, this study provides comprehensive information on how NFAT5 regulates SCTR expression in different osmotic environments.
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PMID:Role of nuclear factor of activated T-cells 5 in regulating hypertonic-mediated secretin receptor expression in kidney collecting duct cells. 2708 Jan 32

The involvement of secretin (SCT) and secretin receptor (SCTR) in regulating body water homeostasis is well established. Identified as one of the vasopressin (Vp)-independent mechanisms in fluid balance, SCT regulates aquaporin 2 (AQP2) in the kidney distal collecting duct cells through activating intracellular cAMP production. This ability to bypass Vp-mediated water reabsorption in kidney implicates SCT's potential to treat nephrogenic diabetes insipidus (NDI). Research on NDI in the past has largely been focused on the searching for mutations in vasopressin receptor 2 (AVPR2), while the functional relationship between SCTR, AVPR2 and NDI remains unclear. Here, we demonstrate the interaction between SCTR and AVPR2 to modulate cellular signaling in vitro. Interestingly, we show in this report that upon heteromer formation with SCTR, R137H, a NDI-causing AVPR2 mutant that is defective in trafficking to cell surface, can functionally be rescued. Our data may provide an explanation for this clinically mild case of NDI, and insights into the pathological development of NDI in the future.
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PMID:Signaling Modification by GPCR Heteromer and Its Implication on X-Linked Nephrogenic Diabetes Insipidus. 2764 63